Stress and Cortisol: The Plague of the 21st Century
James South, M.A.

Stress is an experience as old as humanity, yet the scientific understanding of stress has only developed over the past 70 years. Hungarian scientist Hans Selye pioneered modern stress studies during the 1930s and 40s when he discovered the importance of the adrenal glands in mediating the biological effects of stress.1

Since then science has discovered the LHPA (limbic-hypothalamus-pituitary-adrenal) axis as the neurohormonal regulator of the stress response. Whenever a person experiences something as stressful whether an internal or external stressor emotional reactions (often unconscious) in the limbic system of the brain trigger the hypothalamus to secrete CRH (corticotropin-releasing hormone). The CRH then triggers the pituitary gland to secrete ACTH (adrenocorticotropic hormone), which activates the adrenal glands to produce and release cortisol into the bloodstream.2 Although both CRH and ACTH have stress-mediating roles in their own right, cortisol is the chief stress hormone.

When cortisol blood levels become excessive, this turns off CRH release in a negative feedback loop. Yet as Schimmer and Parker note, Circumstances of stress overcome negative feedback regulation of the HPA axis, leading to a marked rise in the production of corticosteroids [i.e. cortisol].

If the stresses in our life are only occasional, and we take adequate time for rest, relaxation and sleep to restore LHPA equilibrium, then occasional stress cortisol release will not be a problem. Yet if we live a typical modern American lifestyle, we are subject to chronic stress, with inadequate nutrition, rest, relaxation and sleep, and are subject to chronic excessive cortisol levels. It is important to realize that while everyone has the same psychobiologic stress machinery (the LHPA axis), the stressors that can trigger a stress reaction are infinitely variable. As Guyton and Hall point out, almost any type of physical or mental stress can lead within minutes to greatly enhanced secretion of ACTH and consequently cortisol as well, often increasing cortisol secretion as much as 20-fold. Even imaginary stressors, such as fearfully imagining a future event (e.g. an upcoming court trial or IRS audit), can trigger the LHPA axis into stress overreaction.
 

The Dark Side of Cortisol
Since cortisol is an essential stress protection hormone, why should we worry about too much of it? Some cortisol is essential for life. Serious cortisol deficiency produces Addison's disease, a potentially fatal illness. Cortisol is necessary for normal brain, immune, muscle and blood sugar function, and blood circulation. Yet excessive cortisol is equally damaging. Too much cortisol causes abdominal obesity, high blood sugar (adrenal diabetes), muscle wasting, bone loss, immune shutdown, brain (hippocampus) atrophy, poor wound healing, thin wrinkled skin, fluid retention and hypertension. Excessive cortisol frequently causes increased fatigue/decreased energy, irritability, impaired memory, depressed mood, decreased libido, insomnia, anxiety, impaired concentration, crying, restlessness, social withdrawal and feelings of hopelessness.

Chronically excess cortisol may contribute to many diseases, including cancer, ulcers, heart attacks, diabetes, infections, alcoholism, strokes, skin diseases, psychosis, and possibly Parkinson's and Alzheimer's disease, multiple sclerosis and myasthenia gravis. Cortisol excess may contribute to obesity not only because of the metabolic derangements (including insulin resistance) that it promotes, but also because it induces stress overeating, especially (but not only) in women.

Stress (Cortisol) Management
In an ideal world we would make lifelong stress management an integral part of our daily life. We would sleep eight to nine hours nightly. We would take frequent mini-vacations from work to restore LHPA equilibrium. We would eat only nutritious foods, and avoid alcohol and stimulants such as caffeine, pseudoephidrine etc. We would utilize stress reduction techniques such as tai chi, meditation, quiet prayer, massage, etc. We would take brisk 30-to-60-minute walks daily in a pleasant, safe park. We would live in quiet homes without chronic noise stress from loud TVs, stereos, barking dogs, traffic, etc. Our air and water would be clean, and we wouldn't be subject to chemical stressors such as lead, mercury, fluoride, pesticides, environmental estrogens, medical drugs, etc.  Unfortunately, most of us are lucky if we can practice one or two aspects of such an integral stress management lifestyle.
 



Anti-Cortisol Supplements
Fortunately modern scientific research, drawing on ancient systems of medicine, has provided us with supplements that reduce excess cortisol and its many toxic effects. Relora is a proprietary blend of a patented extract from Magnolia officinalis bark and a patent-pending extract from Phellodendron amurense bark, developed by Next Pharmaceuticals.

For centuries Japanese Kampo medicine has used Magnolia bark in herbal remedies such as Saiboku-to to treat clinical depression, anxiety neurosis, insomnia, anxiety, hysteria, stroke and gastrointestinal complaints (all potentially caused by cortisol excess). Two Magnolia bark compounds, magnolol and honokiol, have been identified as the anxiolytic (anti-anxiety) agents in Saiboku-to. Unlike benzodiazepines such as Valium they do not cause CNS depression, excessive muscle relaxation, amnesia or physical dependence. Relora is standardized to a certain level of magnolol and honokiol. In an animal screening model, the two extracts used in Relora demonstrated anxiolytic activity without sedation.

An acute toxicity study using 5,000 mg/kg revealed no significant side effects after 14 days observation. An LD50 (the lethal dose for 50 percent of the test animals) was not able to be established because of the extreme non-toxicity of Relora.

Relora: Human Trials
Fifty stressed people were given 200 mg Relora three times per day for two weeks. Post-trial analysis revealed that 82 percent found Relora effective in controlling stress-induced symptoms, such as depression, anxiety, irritability, emotional ups and downs, concentration difficulties and restlessness. Seventy-eight percent reported increased relaxation, while 74 percent had more restful sleep. No significant side effects were reported, although 24 percent reported some temporary initial drowsiness, and 6 percent reported mild and transient GI upset.

In a second clinical trial, 49 stressed subjects who suffered from stress-induced overeating were given a two-to-three-times per day dose of Relora for two weeks. There was a 76 percent decline in high fat/sugar/salt snack eating. Eighty-four percent reported more restful sleep. The vast majority noted that Relora helped them relax without drowsiness.

In a third trial 12 stressed subjects took Relora for two weeks. Salivary DHEA and cortisol measurements were taken. Morning salivary cortisol levels (when cortisol levels are normally highest) dropped 37 percent, while DHEA levels rose 227 percent. Previously abnormal cortisol/DHEA levels returned to normal in all subjects by the study's end.

Sensoril
Sensoril is a patented proprietary extract of roots and leaves from Withania somnifera Dunn, known as Ashwagandha in Ayurvedic medicine. Developed by researcher Dr. S. Ghosal, who has published many scientific papers on the anti-stress action of various Ashwagandha compounds, Sensoril is standardized to contain the proper amounts of glycowithanolides, Withaferin-A, and oligosaccarides that research has shown to promote optimal anti-stress activity.

Sensoril is a carefully balanced formulation of the key compounds that provide Ashwagandha's immunomodulating and anti-stress activity. By optimizing the ratio of oligosaccharides to polysaccharides, Dr. Ghosal's formulation protects the withanolides from digestive inactivation and enhances their absorption. Ashwagandha has been used in Ayurvedic medicine for many centuries to promote resistance to stress, and to promote health and longevity by increasing resistance to disease, slowing the aging process and revitalizing the body in debilitating conditions. It has also been reported to enhance mental function and memory.

Sensorils extracts have been subject to a wide range of tests to measure anti-stress activity. In one experiment rats were treated with a stress-increasing chemical, PTZ, with or without Sensoril, and then placed in a bright, noisy environment. Control rats got neither PTZ nor Sensoril.

The incidence of defecation and urination under the stressful conditions was the measure of stress. Only 10 percent of the control rats engaged in defecation, 30 percent in stress-induced urination. There was a 90 percent incidence of defecation and 100 percent incidence in urination in the PTZ-only rats. The rats given PTZ and Sensoril had a 20 percent defecation and 40 percent urination incidence, only slightly more than the controls. Another group of rats was forced to swim in inescapable containers for six minutes. When rats give up under stress, they cease vigorous swimming and hang motionless, with their noses just above water. The stress-induced immobility period for the control rats was 188 seconds, but only 122 seconds for the Sensoril-treated rats.

In yet another rat study, restraint stress induced stress ulcers. One hundred percent of the control rats developed ulcers, yet only 20 percent of the Sensoril rats developed ulcers. The rats group score, a composite of the number and severity of the ulcers, was 46 for the control rats and 10.6 for the Sensoril rats.

Rats were exposed to severe overcrowding conditions or tactile stress (continuous poking), and then given morphine. Seventy percent of the tactile-stressed and 100 percent of the overcrowding-stressed control rats developed convulsions, and 80 percent and 90 percent died, respectively. Yet only 10 percent of the tactile-stressed rats and 10 percent of the overcrowding-stressed rats given morphine plus Sensoril developed convulsions, while 0 percent and 10 percent died.

Another experiment focused on the effects of stress on the adrenal glands. Some rats were restrained; some were not. Some of the restraint-stress rats were given Sensoril; some were not. Then animals were sacrificed, and their adrenal glands extracted and weighed. The content of vitamin C and corticosterone (the rat equivalent of cortisol) were measured. Severe stress causes adrenal glands to enlarge, and their vitamin C and corticosterone content drops. The C is used up in making corticosterone and the corticosterone is released in response to stress. The unstressed control rats had an average adrenal weight of 25.4 mg/100 grams body weight.

The restraint-stressed rats without Sensoril had an adrenal weight of 34.2, while the restraint-stressed rats with Sensoril had an adrenal weight of 22.5. The control rats had 298 mcg vitamin C/100 mg adrenal weight, and 3.9 mcg corticosterone/100 mg adrenal weight. The restraint-stressed rats without Sensoril had only 126 mcg C, and 1.4 mcg corticosterone, a clear measure of their severe stress. The restraint-stressed-plus-Sensoril rats had 272 mcg C and 4.4 mcg corticosterone.

The fact that the restraint-stressed Sensoril rats had smaller adrenal glands with more corticosterone in them than the unstressed control rats, and almost as much C, shows that biologically speaking, the Sensoril/stressed rats were actually less stressed than the unstressed control rats!

Other studies have shown the ability of Sensoril to reduce morphine-stress-induced immunodepression, and to increase immune activity and learning and memory in both young and old rats under stressful conditions. Sensoril has increased the brain antioxidant enzymes SOD, catalase, and glutathione peroxidase in a manner similar to deprenyl. It has also reduced the brain damage caused by haloperidol, an anti-psychotic medication noted for causing a neurodisorder called tardive dyskinesia.

Cortisol Control Formula: Relora Plus Sensoril
Given the excellent safety profile of the active ingredients in Relora and Sensoril, their use for centuries in Oriental medicine and their modern scientific validation, it makes sense to combine them to create a potent anti-stress supplement known as Cortisol Control Formula. Each Cortisol Control Formula capsule contains 250 mg Relora and 75 mg Sensoril. The recommended dose is one capsule three times per day. Cortisol Control should not be combined with alcohol. It should not be taken with prescription psychiatric drugs, such as Valium or other benzodiazepines, without physician approval. Cortisol Control is not intended for use by children under 18, or pregnant or lactating women.

Relora is already a widely used, popular stress-management supplement. Naturopathic physician James LaValle has reported excellent results with its use in his practice. The new combination of Relora and Sensoril should prove even more effective in helping to alleviate stress overload, the scourge of our modern 24/7 hyper-drive world.
 

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References:
1. Selye, H.   The evolution of the stress concept.  Amer Sci 1973, 61: 692-99.

2. Carpenter, W. et al.  Cortisol s effects on human mental functioning.  J Clin Psychopharmacol 1982, 2: 91-101.

3. Hardman, J. and Limbird, L., eds. Goodman and Gilman s The Pharmacological Basis of Therapeutics. NYC: McGraw-Hill; 1996:1464.

4. Guyton, A. and Hall, J. Textbook of Medical Physiology. Philadelphia: W.B. Sanders; 2000: 869-83.

5. Sapse, A.  Stress, cortisol, interferon and  stress  diseases.  Med Hypoth 1984, 13: 31-44.

6. Starkman, M. and Schteingart, D.  Neuropsychiatric manifestations of patients with Cushing s syndrome.  J Clin Psych 1981, 141: 215-19.

7. Epel, E. et al.  Stress may add bite to appetite in women: a laboratory study of stress-induced cortisol and eating behavior.  Psychoneuroendocrinol 2001, 26: 37-49.

8. Maruyama, Y. and Kuribara, H.  Overview of the pharmacological features of Honokiol.  CNS Drug Rev 2000, 6: 35-44.

9. Sufka, K. et al.  Anxiolytic properties of botanical extracts in the chick social separation-stress procedure  Psychopharmacol 2001, 153: 219-24

10. LaValle, J. and Hawkins, E. Relora The Natural Breakthrough to Losing Stress-Related Fat and Wrinkles. North Bergen, NJ: Basic Health Publications; 2003: 16.

11. Bhattacharya, S. et al.  Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera.  Phytother Res 1987, 1: 32-37.

12. Ramarao, P. et al.  Effects of glycowithanolides from Withania somnifera on morphine-induced inhibition of intestinal motility and tolerance to analgesia in mice.  Phytother Res 1995, 9: 66-68.

13. Ghosal, S. et al.  Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera.  Phytother Res 1989, 3: 201-06.

14. Bhattacharya, S. et al.  Antioxidant activity of glycowithanolides from Withania somnifera.  Ind J Exper Biol 1997, 35: 236-39.

15. Naidu, P. et al.  Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action..  J Medicinal Food 2003, 6: 107-14.

16. LaValle, J. and Yale, S. Cracking the Metabolic Code. North Bergen, NJ: Basic Publications; 2004: 126.
 

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